Search results

1

Determination of cytokine profiles in populations of dendritic cells from cattle infected with bovine leukaemia virus

100%

Iwan E., Szczotka M., Kocki J., Pluta A., Iwan E., Szczotka M., Kocki J., Pluta A.

Polish Journal of Veterinary Sciences

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2018

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vol. 21

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issue 4

2

Evaluation of immature monocyte-derived dendritic cells generated from patients with colorectal cancer

100%

Maciejewski R., Radej S., Furmaga J., Chrościcki A., Rudzki S., Roliński J., Wallner G.

Polish Journal of Surgery

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2013

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vol. 85

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issue 12

714-720

EN

Dendritic cells are heterogeneous population of the leukocytes and most potent APC in activation of naive T lymphocytes. Therefore the DCs generated in vitro are under research for their application in anti-tumor immunotherapy. The aim of the study was generation of the immature dendritic cells from peripheral blood monocytes collected from colorectal cancer patients and comparison of their ability to endocytosis, cytokine production and immunophenotype to DCs generated from healthy donors. Material and methods. 16 adenocarcinoma stage II patients were included in the study. Dendritic cells were generated in the presence of rhGM-CSF and IL-4. PBMC were isolated from the blood of patients and 16 healthy donors - control group. Immunophenotype, ability of endocytosis of Dextran- FITC as well as intracellular IL-12 expression of the generated dendritic cells was measured using flow cytometry. The cytokines (IL-6, IL-10, IL-12p70, IFN-γ) concentration in the supernatants of DCs culture was measured by ELISA. Results. The percentage of the immature dendritic cells and expression of CD206 and CD209 antigens was significantly higher in patients group (p <0.05 and p <0.001 respectively). Significantly (p <0.001) higher expression of the antigens which initiate the Th2 immune response (CD80-/CD86 + and B7-H2 + / CD209 +) was in the patients group. There were no differences in endocytosis ability and the cytokines (IL-6, IL-10, IL-12p70, IFN-γ) concentration between investigated groups. Conclusions. High immature markers expression on the generated dendritic cells together with identical endocytosis ability in patients group is advantageous in antitumor autologous cells immunotherapy planning. However there is one troubling fact - high expression of markers, which may induce tolerance to particular antigen. It seems to be more reasonable to use the autologous DCs in the antitumor immunotherapy, especially due to the incompatibility in allogenic cells in the context of HLA complex.

3

Tumors and the danger model.

100%

Kowalczyk D. W.

Acta Biochimica Polonica

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2002

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vol. 49

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issue 2

295-302

EN

This article reviews the evidence for the danger model in the context of immune response to tumors and the insufficiency of the immune system to eliminate tumor growth. Despite their potential immunogenicity tumors do not induce significant immune responses which could destroy malignant cells. According to the danger model, the immune surveillance system fails to detect tumor antigens because transformed cells do not send any danger signals which could activate dendritic cells and initiate an immune response. Instead, tumor cells or antigen presenting cells turn off the responding T cells and induce tolerance. The studies reviewed herein based on model tumor antigens, recombinant viral vectors and detection of tumor specific T cells by MHC/peptide tetramers underscore the critical role of tumor antigen presentation and the context in which it occurs. They indicate that antigen presentation only by activated but not by cancer or resting dendritic cells is necessary for the induction of immune responses to tumor antigens. It becomes apparent that the inability of dendritic cells to become activated provides a biological niche for tumor escape from immune destruction and seems to be a principal mechanism for the failure of tumor immune surveillance.

4

Cancer immunotherapy using cells modified with cytokine genes.

88%

Kowalczyk D. W., Wysocki P. J., Mackiewicz A.

Acta Biochimica Polonica

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2003

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vol. 50

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issue 3

613-624

EN

The ability of various cytokines to hamper tumor growth or to induce anti-tumor immune response has resulted in their study as antitumor agents in gene therapy approaches. In this review we will concentrate on the costimulation of antitumor immune responses using modification of various cell types by cytokine genes. Several strategies have emerged such as (i) modification of tumor cells with cytokine genes ex vivo (whole tumor cell vaccines), (ii) ex vivo modification of other cell types for cytokine gene delivery, (iii) delivery of cytokine genes into tumor microenvironment in vivo, (iv) modification of dendritic cells with cytokine genes ex vivo. Originally single cytokine genes were used. Subsequently, multiple cytokine genes were applied simultaneously, or in combination with other factors such as chemokines, membrane bound co-stimulatory molecules, or tumor associated antigens. In this review we discuss these strategies and their use in cancer treatment as well as the promises and limitations of cytokine based cancer gene therapy. Clinical trials, including our own experience, employing the above strategies are discussed.

5

Immunomodelling Characteristics of Mature Dendritic Cells Stimulated by Colon Cancer Cells Lysates

88%

Radej S., Roliński J., Rawicz-Pruszyński K., Bury P., Borowski G., Furmaga J., Chrościcki A., Wallner G., Maciejewski R.

Polish Journal of Surgery

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2015

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vol. 87

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issue 2

71-82

EN

Application of cells with high TAA (tumor associated antigen) presentation potential seems to be crucial in neoplasia immunotherapy. Such feature is distributed in dendritic cells, which present peptides from processed TAA - MHC molecules complex to the T cells of a host. The aim of the study was to assess the influence of colon neoplasia tissue lysate on functioning of generated autologous DC’s in the field of autologous CD4+ lymphocytes immunological response towards Th1/Th2 under in vitro environment together with comparison and assessment of DCs’ immunosuppressive properties acquired from patients with colon cancer. Material and methods. The population of this study consisted of 16 healthy- controls, 36colon cancer patients. Blood samples were collected 24h before planned surgery and preventive antibiotic therapy. Neoplastic tissue sample, was digested for cell lysates preparation. DC’s generation from PBMC was carried out in standard conditionsand medium enriched with rhGM-CSF and rhIL-4. Mature DC`s and cocultured autologous CD4 lymphocytes immunophenotype assessment was analyzed with flow cytometer. Intracellular and culture medium cytokines concentration was analyzed with ELISA and FACS method. Results. DC`s generated from colon cancer patients stimulated with lysates presented greater maturity, lower expression of CD206 antigen, significantly higher expression of HLA-DR, CD208 and CD209 and high intracellular expression of IL-12, compared to non-stimulated cells. Conclusions. The neoplastic tissue in vivo produces a number of substances having an unfavorable effect on immune system, our results suggests using lysates as good dendritic cells stimulators that possibly could have application in colon cancer immunotherapy

6

CD40 stimulation induces differentiation of acute lymphoblastic leukemia cells into dendritic cells

88%

Łuczyński W., Stasiak-Barmuta A., Iłendo E., Krawczuk-Rybak M., Malinowska I., Mitura-Lesiuk M., Parfieńczyk A., Szymański M.

Acta Biochimica Polonica

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2006

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vol. 53

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issue 2

377-382

EN

Despite the very high percentage of long-term remissions in acute lymphoblastic leukemia (ALL) in children, some of them suffer from recurrence of the disease. New treatment modalities, e.g. effective geno- and immunotherapy are needed. The use of neoplasmatic cells to present tumor antigens is one of the approaches in cancer vaccines. ALL cells lack the expression of costimulatory molecules and are poor antigen presenting cells (APCs) for T-cell activation. CD40/40L interaction stimulates B-cells to proliferate, differentiate, upregulate costimulatory molecules and increase antigen presentation. The aim of the study was to test the hypothesis that ALL cells can be turned into professional APCs by CD40L activation. Children with B-cell precursor ALL were enrolled into the study. Mononuclear cells from bone marrow or peripheral blood were stimulated with CD40L and interleukin 4. Results: 1) after culture we noted upregulation of all assessed costimulatory, adhesion and activatory molecules i.e. CD1a, CD11c, CD40, CD54, CD80, CD83, CD86, CD123, HLA class I and II; 2) CD40L activated ALL cells induced proliferation of allogeneic T-cells (measured by [3H]thymidine incorporation). These results confirm the possibility of enhancing the immunogenicity of ALL cells with the CD40L system and indicate that this approach can be used in immunotherapeutic trials.

7

Nonviral transfection of human umbilical cord blood dendritic cells is feasible, but the yield of dendritic cells with transgene expression limits the application of this method in cancer immunotherapy

75%

Markowicz S., Niedzielska J., Kruszewski M., Ołdak T., Gajkowska A., Machaj E. K., Skurzak H., Pojda Z.

Acta Biochimica Polonica

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2006

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vol. 53

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issue 1

203-212

EN

Dendritic cells (DC) generated from human umbilical cord blood might replace patients' DC in attempts to elicit tumor-specific immune response in cancer patients. We studied the efficiency of transfection of human cord blood DC with plasmid DNA carrying the enhanced version of green fluorescent protein (EGFP) as a reporter gene, to test if nonviral gene transfer would be a method to load DC with protein antigens for immunotherapy purposes. Cord blood mononuclear cells were cultured in serum-free medium in the presence of granulocyte-monocyte colony stimulating factor (GM-CSF), stem cell factor (SCF) and Flt-3 ligand (FL), to generate DC from their precursors, and thereafter transfected by electroporation. Maturation of DC was induced by stimulation with GM-CSF, SCF, FL and phorbol myristate acetate (PMA). Transfected DC strongly expressed EGFP, but transfection efficiency of DC, defined as HLA-DR+ cells lacking lineage-specific markers, did not exceed 2.5%. Expression of the reporter gene was also demonstrated in the DC generated from transfected, purified CD34+ cord blood cells, by stimulation with GM-CSF, SCF, FL, and tumor necrosis factor α (TNF-α). Transfection of CD34+ cells was very efficient, but proliferation of the transfected cells was much reduced as compared to the untransfected cells. Therefore, the yield of transgene-expressing DC was relatively low. In conclusion, nonviral transfection of cord blood DC proved feasible, but considering the requirements for immunotherapy in cancer patients, transfection of differentiated DC or generation of DC from transfected hematopoietic stem cells provide only a limited number of DC expressing the transgene.

8

The balance between pro- and anti-inflammatory cytokines in the immune responses to BCG and DTwP vaccines

75%

Druszczynska M., Kowalewicz-Kulbat M., Maszewska A., Rudnicka K., Szpakowski P., Wawrocki S., Wlodarczyk M., Rudnicka W.

Acta Biochimica Polonica

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2015

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vol. 62

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issue 4

913-921

EN

Bacillus Calmette-Guérin (BCG) and pertussis vaccines have been found to be insufficient and their further improvement is required. In order to develop improved vaccines, a better understanding of the main pathways involved in the host's protective immunity to the pathogens is crucial. We address the question as to whether the balance between pro- and anti-inflammatory cytokine production might affect the host responses to BCG and diphtheria-tetanus toxoids-whole cell pertussis (DTwP) vaccines. The study population consisted of 118 healthy people, age range 18-30 years, who had been subjected to BCG and DTwP vaccination according to the state policy. Tuberculin skin testing (TST) revealed a delayed type hypersensitivity (DTH) to PPD (purified protein derivative) in 53% volunteers. The variability in development of the BCG-driven DTH to tuberculin prompted us to address a question as to whether Th1/Th2 polarization is involved in the lack of skin responsiveness to PPD. PPD-stimulated blood lymphocytes from TST+ participants produced significantly more IFN-γ and less IL-10 than lymphocytes from TST- volunteers. However, TST- volunteers' sera contained more anti-pertussis IgG but not anti-diphtheria toxin IgG. Mycobacterial antigens and particularly PPD induced a higher expression of HLA-DR and co-stimulatory CD80 receptors on DCs from TST+ than TST- participants. BCG but not PPD pulsed DCs from TST- volunteers produced significantly more IL-10. Mycobacterial antigen stimulated DCs from TST+ volunteers induced a more intense IFN-γ production in co-cultures with autologous lymphocytes than the cells from TST- participants. Differences among the types of dendritic cell activities contribute to development of tuberculin reactivity in BCG vaccinated volunteers.

Refine search results

Determination of cytokine profiles in populations of dendritic cells from cattle infected with bovine leukaemia virus

Evaluation of immature monocyte-derived dendritic cells generated from patients with colorectal cancer

Tumors and the danger model.

Cancer immunotherapy using cells modified with cytokine genes.

Immunomodelling Characteristics of Mature Dendritic Cells Stimulated by Colon Cancer Cells Lysates

CD40 stimulation induces differentiation of acute lymphoblastic leukemia cells into dendritic cells

Nonviral transfection of human umbilical cord blood dendritic cells is feasible, but the yield of dendritic cells with transgene expression limits the application of this method in cancer immunotherapy

The balance between pro- and anti-inflammatory cytokines in the immune responses to BCG and DTwP vaccines